Abnormal neural connectivity is increasingly thought to be key contributor to the neurobiology of autism. The cerebellum is one of the most widely connected structures in the central nervous system, and it is also the most consistent site of brain abnormality in autism. The most common defect is a reduced number of Purkinje cells (PC), which will drastically impact connectivity within the cerebellum and between the cerebellum and other brain regions. PC reduction will disinhibit excitatory output leaving the cerebellum for other brain regions. Such aberrant activity may in turn lead to the abnormal strengthening of anatomic connections and the emergence of aberrant functional connectivity with limbic, thalamic, and cerebrocortical sites. This will disrupt the cerebellum's ability to coordinate cognitive and socioemotional behaviors, thereby contributing to many of the deficits characteristic of autism. To investigate cerebellar connectivity in autism, we will employ diffusion tensor imaging (DTI), an MRI method that allows the quantification of white matter tract structure, and functional connectivity magnetic resonance imaging (FCMRI), which assesses interregional coherence of MRI signal change as an index of functional connectivity. DTI and FCMRI will be used to examine the anatomic and functional integrity of cerebellar connections with limbic, thalamic, and cerebrocortical sites in individuals with autism spectrum disorders and in healthy controls. Connectivity measures will be correlated with volumes of specific cerebellar sub-regions to assess the impact of anatomic abnormality on connectivity. We will also investigate associations between these anatomic and connectivity measures and independent measures of cerebellar function. PUBLIC HEALTH RELEVANCE: Findings from this study will improve our understanding of the neural basis of autism. Such should lead to better-informed treatments, and it should focus the search for the etiology of this common and devastating neurodevelopmental disorder.